Efforts to understand the interactions of drugs and toxins with DNA as well as the desire for new methods of DNA manipulation have spurred the design and synthesis of small molecules that bind in specific ways to DNA.
The biogenic polyamines (putrescine, spermidine, spermine) bind primarily in the minor groove and are thought to hydrogen bond with donor atoms on the edges of the base pairs rather than associating with the phosphate backbone..sup.1 Studies of simple aliphatic polyamines.sup.2 suggest that the three- to four-carbon spacing between ammonium groups is nearly ideal for matching the spacing of base pairs along the minor groove ladder while ensuring full protonation of the amines at pH 7.
The naturally occurring steroidal diamines such as irehdiamine A, malouetine, dipyrandium, and chonemorphine bearing ammonium groups at C3 and C17 (or the adjacent carbon, C20) of the steroid are amphiphilic in nature, presenting a large hydrophobic group between the cationic extremities..sup.3 Their biophysical features include unwinding of superhelical DNA, increasing the duplex denaturation temperature, and altering of the UV and CD spectra of DNA while such biochemical functions as aiding in membrane permeability, ion transport, and DNA replication and multagenesis are also observed..sup.4 For dipyrandium, binding to DNA is proposed to occur in the minor groove in conjunction with 5'-d(TA) kinks..sup.5
A lipospermine for gene transfer is marketed in Europe under the name transfectam (Prolabo).
The steroidal diamines, as well as the recently reported steroidal spermidine, squalamine, isolated from sharks, are of considerable interest as antibiotics..sup.6